In this study, we have produced soluble versions of just the HIV-1 Env gp120 receptor binding domain derived from a primary isolate stabilized by heterologous trimerization motifs (GCN4). A variant of the wild-type gp120 was generated similarly. This variant contained a mutation on the center of the CD4 binding site known as the "Phe 43 cavity". This mutation stabilized the CD4-state of gp120 and increased CD4 affinity 10-to-20-fold. We have produced milligram quantities of these proteins and and performed a detailed biochemical and biophysical analysis. We have tested these glycoproteins for immunogenicity in rabbits. Breadth of neutralization indicated that the CD4-state trimers elicited an enhanced neutralizing profile compared to wild-type glycoprotein trimers are interesting platforms for further modification to better elicit broadly neutralizing antibodies (published). A second goal of this study is to obtain crystal structures of these trimeric HIV-1 gp120 glycoproteins. Dr. Pancera will conduct structural studies on these proteins as well as full length gp120 glycoproteins that she has produced in the Wyatt laboratory as part of her doctoral studies (completed April 2005).